2-aminopyridine derivatives as plant growth regulating compounds

Abstract

 The present invention relates to non-steroidal brassinosteroid mimetic derivatives of formula (I), to processes and intermediates for preparing them, to plant growth regulator compositions comprising them and to methods of using them for controlling the growth of plants and/or promoting the germination of seeds.

Description

[0001] The present invention relates to novel non-steroidal brassinosteroid mimetic derivatives, to processes and intermediates for preparing them, to plant growth regulator compositions comprising them and to methods of using them for controlling the growth of plants and/or promoting the germination of seeds.

[0002] Various chemical derivatives that act on the brassinosteroid signalling pathway have been described, for example, in Bioorg. Med. Chem. (1998), 6, p.1975; Bioorg. Med. Chem. Let. (1999), 9, p.425; J. Agric. Food Chem. (2002), 50, p. 3486; Planta (2001), 213, p.716; WO2008/049729, WO2009/109570 and Chemistry & Biology (2009), 16, p.594-604. Brassinosteroids and analogs thereof have been described to have useful plant growth regulating properties.

[0003] It has now surprisingly been found that certain new non-steroidal brassinosteroid mimetic derivatives have properties that are useful for controlling the growth of plants and/or promoting the germination of seeds. Preferably, the new compounds may result in improved plant growth properties, such as faster growth, faster germination, earlier germination and / or reduced toxicity. The compounds may offer other advantages such as enhanced solubility, or be more advantageously formulated, provide more efficient delivery to the plant, provide improved uptake into the plant, or be more readily biodegradable.

[0004] According to the present invention, there is provided a compound of formula (I)

wherein

R₁, R₂ are independently H, C₁-C₆haloalkyl, C₁-C₆alkoxy, cyano, halogen, C₁-C₆alkyl or C₁-C₆alkyl substituted by one or more hydroxyl, amine;

X is halogen, C₁-C₆haloalkyl, cyano, thiocyanate, nitro, amine, C₁-C₆alkoxy, C₁-C₆haloalkoxy, C₁-C₆alkylthio, C₁-C₆haloalkylthio, C₁-C₆alkylsulfinyl, C₁-C₆haloalkylsulfinyl, C₁-C₆alkylsulfonyl, C₁-C₆haloalkylsulfonyl, C₂-C₆alkenyl, C₂-C₆alkynyl, C2-C6 haloalkenyl, C2-C6 haloalkynyl C₁-C₆alkylcarbonyl, C₁-C₆alkoxycarbonyl, C₁-C₆haloalkoxycarbonyl, C₁-C₆haloalkylcarbonyl, C₃-C₈cycloalkyl, formyl, mercapto; or X is heteroaryl or heteroaryl subtituted by one or more halogen, cyano, C₁-C₃alkyl, C₁-C₃haloalkyl;

Or X is an amine group mono- or di-substituted by hydroxyl, C₁-C₆alkyl, C₂-C₆alkenyl, C₂-C₆alkynyl, C₁-C₆haloalkyl, C₁-C₆alkoxy, C₁-C₆haloalkoxy, C₃ to C₈cycloalkyl;

Or X is an amine group mono- or di-substituted by C₁-C₆alkyl substituted by one or more halogen, cyano, nitro, aryl, or aryl subtituted by one or more R10; C₂-C₆alkenyl substituted by one or more R10; or C₂-C₆alkynyl substituted by one or more R10,

Or X is an amine group mono- or di-substituted by heterocyclyl or heterocyclyl subtituted by one or more R10;

Or X is an amine group mono or di-substituted by an aryl or an aryl subtituted by one or more R10;

R₃ is H, C₁-C₆alkyl, C₁-C₆haloalkyl, C₁-C₆alkylcarbonyl, C₁-C₆alkoxycarbonyl;

or R₃ is C₁-C₆alkyl substituted by one or more cyano, amine, carbonylamine;

Q is a group according to formula (I')

Or R₃ and Q form a cyclic group according to formula (I")

wherein,

both W are independently O or S;

R₅, R₆, R₇ and R₈ are independently hydrogen, halogen, nitro, cyano, C₁-C₆alkyl, C₁-C₆haloalkyl, C₁-C₆alkoxy, hydroxyl, -OC(O)R₁₁, amine, N- C₁-C₆alkyl amine, or N,N-di-C₁-C₆ alkyl amine;

R₁₁ is hydrogen, C₁-C₆ alkyl, C₁-C₆ alkoxy, or C₁-C₆ haloalkyl;

R₉ is hydrogen, C₁-C₆ alkyl, C₁-C₆ haloalkyl, C₂-C₆ alkenyl, C₂-C₆ haloalkenyl, C₂-C₆ alkynyl, C₂-C₆ haloalkynyl, C₃-C₇ cycloalkyl, aryl or aryl substituted by one to five substituents R₁₀, heterocyclyl or heterocyclyl substituted by one to five substituents R₁₀;

or R₉ is C₁-C₆alkyl substituted by one or more cyano, nitro, amine, hydroxyl, C₁-C₆ alkoxy, C₁-C₆ haloalkoxy, C₁-C₆ alkylthio, C₁-C₆ haloalkylthio, C₁-C₆ alkylsulfinyl, C₁-C₆ haloalkylsulfinyl, C₁-C₆ alkylsulfonyl, C₁-C₆ haloalkylsulfonyl, C₃-C₇ cycloalkyl, N-C₁-C₆ alkyl amine, N,N-di-C₁-C₆ alkyl amine, aryl or aryl substituted by one to five substituents R₁₀, heterocyclyl or heterocyclyl substituted by one to five substituents R₁₀;

each R₁₀ is independently cyano, nitro, amino, hydroxyl, halogen, C₁-C₆ alkyl, C₁-C₆ haloalkyl, C₂-C₆ alkenyl, C₂-C₆ haloalkenyl, C₂-C₆ alkynyl, C₂-C₆ haloalkynyl, C₃-C₆ cycloalkyl, C₃-C₆ halocycloalkyl, C₁-C₆ alkoxy, C₁-C₆ haloalkoxy, C₁-C₆ alkylthio, C₁-C₆ haloalkylthio, C₁-C₆ alkylsulfinyl, C₁-C₆ haloalkylsulfinyl, C₁-C₆ alkylsulfonyl, C₁-C₆ haloalkylsulfonyl, N-C₁-C₆ alkylamino, N,N-di-(C₁-C₆ alkyl)amino, N,N-di-(C₁-C₆ alkyl)aminocarbonyl, N,N-di-(C₁-C₆ alkyl)aminosulfonyl, C₁-C₆ alkylcarbonyl, C₁-C₆ alkylcarbonyloxy, C₁-C₆ alkoxycarbonyl, C₁-C₆ alkylcarbonylamino;

[0005] The compounds of formula (I) may exist in different geometric or optical isomers (diastereoisomers and enantiomers) or tautomeric forms. This invention covers all such isomers and tautomers and mixtures thereof in all proportions as well as isotopic forms such as deuterated compounds. The invention also covers all salts, N-oxides, and metalloidic complexes of the compounds of formula (I).

[0006] Each alkyl moiety either alone or as part of a larger group (such as alkoxy, alkoxycarbonyl, alkylcarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl) is a straight or branched chain and is, for example, methyl, ethyl, n-propyl, n-butyl, n-pentyl, n-hexyl, iso-propyl, n-butyl, sec-butyl, iso-butyl, tert-butyl or neo-pentyl. The alkyl groups are preferably C₁ to C₆ alkyl groups, more preferably C₁-C₄ and most preferably C₁-C₃ alkyl groups.

[0007] Each alkenyl moiety either alone or as part of a larger group (such as alkoxy, alkoxycarbonyl, alkylcarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl) is having at least one carbon-carbon double bond and is, for example, vinyl, allyl. The Alkenyl groups are preferably C₂ to C₆alkenyl groups, more preferably C₂-C₄alkenyl groups.

[0008] Each alkynyl moiety either alone or as part of a larger group (such as alkoxy, alkoxycarbonyl, alkylcarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl) is having at least one carbon-carbon triple bond and is, for example, ethynyl, propargyl. The Alkynyl groups are preferably C₂ to C₆alkynyl groups, more preferably C₂-C₄alkynyl groups. The term "alkynyl", as used herein, unless otherwise indicated, includes alkyl moieties having at least one carbon-carbon triple bond wherein alkyl is as defined above.

[0009] Halogen is fluorine (F), chlorine (Cl), bromine (Br) or iodine (I).

[0010] Haloalkyl groups (either alone or as part of a larger group, such as haloalkoxy or haloalkylthio) are alkyl groups which are substituted with one or more of the same or different halogen atoms and are, for example, -CF₃, -CF₂Cl, -CH₂CF₃ or -CH₂CHF₂.

[0011] Hydroxyalkyl groups are alkyl groups which are substituted with one or more hydroxyl group and are, for example, -CH₂OH, -CH₂CH₂OH or -CH(OH)CH₃.

[0012] In the context of the present specification the term "aryl" refers to a ring system which may be mono-, bi- or tricyclic. Examples of such rings include phenyl, naphthalenyl, anthracenyl, indenyl or phenanthrenyl. A preferred aryl group is phenyl.

[0013] An "amine group" refers to a group of the structure -NR'R", wherein R' and R" are individually hydrogen or substituents as appropriate or unless otherwise indicated.

[0014] Unless otherwise indicated, alkenyl and alkynyl, on their own or as part of another substituent, may be straight or branched chain and may preferably contain 2 to 6 carbon atoms, preferably 2 to 4, more preferably 2 to 3, and where appropriate, may be in either the (E)- or (Z)-configuration. Examples include vinyl, allyl and propargyl.

[0015] Unless otherwise indicated, cycloalkyl may be mono- or bi-cyclic, may be optionally substituted by one or more C₁-C₆alkyl groups, and preferably contain 3 to 7 carbon atoms, more preferably 3 to 6 carbon atoms. Examples of cycloalkyl include cyclopropyl, 1-methylcyclopropyl, 2-methylcyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl.

[0016] Each W is independently O or S. Preferably both W are the same. More preferably both W are O.

[0017] The term "heterocyclyl" is defined to include saturated heterocyclyl as well as heteroaryl and in addition their unsaturated or partially unsaturated analogues such as 4,5,6,7-tetrahydro-benzothiophenyl, 9H-fluorenyl, 3,4-dihydro-2H-benzo-1,4-dioxepinyl, 2,3-dihydro-benzofuranyl, piperidinyl, 1,3-dioxolanyl, 1,3-dioxanyl, 4,5-dihydro-isoxazolyl, tetrahydrofuranyl and morpholinyl.

[0018] The term "heteroaryl" refers to an aromatic ring system containing at least one heteroatom and consisting either of a single ring or of two or more fused rings. Preferably, single rings will contain up to three and bicyclic systems up to four heteroatoms which will preferably be chosen from nitrogen, oxygen and sulfur. Examples of such groups include pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, furanyl, thiophenyl, oxazolyl, isoxazolyl, oxadiazolyl, thiazolyl, isothiazolyl, thiadiazolyl, pyrrolyl, pyrazolyl, imidazolyl, triazolyl and tetrazolyl. A preferred heteroaryl group is pyridine.

[0019] Preferred values of Q, W, R₁, R₂, R₃, R₅, R₆, R₇, R₈, R₉ and X of the compound of formula I are, in any combination, as set out below:

Q is (I_');

Both W are O;

R₁ is H, trifluoromethyl, cyano, halogen or methyl;

R₂ is H, trifluoromethyl, cyano, methoxy, halogen or methyl;

X is halogen, C₁-C₆haloalkyl or cyano;

R₃ is H or C₁-C₆alkyl;

R₅, R₆, R₇ and R₈ are independently hydrogen or methyl;

R₉ is hydrogen, C₁-C₆alkyl, C₁-C₆haloalkyl, C₂-C₆ alkenyl, C₂-C₆alkynyl, C₃-C₆cycloalkyl, benzyl;

or R₉ is C₁-C₆ alkyl substituted by one or more C₁-C₆alkoxy, C₁-C₆alkylthio;

[0020] More preferably, R₁ is H or methyl. Most preferably, R₁ is H.
More preferably, R₂ is H or methyl. Most preferably, R₂ is H.
More preferably, X is bromine, chlorine, trifluoromethyl or cyano.
More preferably, R₃ is H.
More preferably, R₅, R₆, R₇ and R₈ are H.
More preferably R₉ is hydrogen, methyl, ethyl, n-propyl or iso-propyl. Even more preferably, R₉ is hydrogen, methyl or ethyl. Most preferably, R₉ is hydrogen or methyl.
Any combinations of preferred features are herewith disclosed.

[0021] Thus, the more preferred values of Q, W, R₁, R₂, R₃, R₅, R₆, R₇, R₈, R₉ and X of the compound of formula I are, in any combination, as set out below:

Q is (I');

Both W are O;

R₁ is H or methyl;

R₂ is H or methyl;

X is bromine, chlorine, trifluoromethyl or cyano;

R₃, R₅, R₆, R₇ and R₈ are hydrogen;

R₉ is hydrogen, methyl, ethyl, n-propyl or iso-propyl.

[0022] Thus, the most preferred values of Q, W, R₁, R₂, R₃, R₅, R₆, R₇, R₈, R₉ and X of the compound of formula I are, in any combination, as set out below:

Q is (I');

Both W are O;

X is bromine, chlorine, trifluoromethyl or cyano;

R₁, R₂, R₃, R₅, R₆, R₇ and R₈ are hydrogen;

R₉ is hydrogen or methyl;

[0023] In an alternative set of embodiments, preferred values of Q, W, R₁, R₂, R₃, R₅, R₆, R₇, R₈, and X of the compound of formula I are, in any combination, as set out below:

Q and R₃ form the cyclic group (I");

Both W are O;

R₁ is H, trifluoromethyl, cyano, halogen or methyl;

R₂ is H, trifluoromethyl, cyano, methoxy, halogen or methyl;

X is halogen, C₁-C₆haloalkyl or cyano;

R₅, R₆, R₇ and R₈ are independently hydrogen or methyl.

[0024] More preferably, R₁ is H or methyl. Most preferably, R₁ is H.
More preferably, R₂ is H or methyl. Most preferably, R₂ is H.
More preferably, X is bromine, chlorine, trifluoromethyl or cyano.
More preferably, R₅, R₆, R₇ and R₈ are H.
Any combinations of preferred features are herewith disclosed.

[0025] Thus, the more preferred values of Q, W, R₁, R₂, R₃, R₅, R₆, R₇, R₈ and X of the compound of formula I are, in any combination, as set out below:

Q and R₃ form the cyclic group (I");

Both W are O;

R₁ is H or methyl;

R₂ is H or methyl;

X is bromine, chlorine, trifluoromethyl or cyano;

R₅, R₆, R₇ and R₈ are hydrogen.

[0026] Thus, the most preferred values of Q, W, R₁, R₂, R₃, R₅, R₆, R₇, R₈ and X of the compound of formula I are, in any combination, as set out below:

Q and R₃ form the cyclic group (I");

Both W are O;

X is bromine, chlorine, trifluoromethyl or cyano;

R₁, R₂, R₃, R₅, R₆, R₇ and R₈ are hydrogen.

[0027] Table 1 below includes examples of compounds of formula (Ia) wherein W is O and R₁, R₂, R₃, R₅, R₆, R₇, R₈, R₉ and X are as defined.

Table 1

Compound	X	R1	R2	R3	R5	R6	R7	R8	R9
1.00	CN	H	H	H	H	H	H	H	CH3
1.01	CF3	H	H	H	H	H	H	H	CH3
1.02	Br	H	H	H	H	H	H	H	CH3
1.03	Cl	H	H	H	H	H	H	H	CH3
1.04	I	H	H	H	H	H	H	H	CH3
1.05	CN	H	H	H	H	H	H	H	H
1.06	CF3	H	H	H	H	H	H	H	H
1.07	Br	H	H	H	H	H	H	H	H
1.08	Cl	H	H	H	H	H	H	H	H
1.09	I	H	H	H	H	H	H	H	H
1.10	CN	H	CH3	H	H	H	H	H	CH3
1.11	CF3	H	CH3	H	H	H	H	H	CH3
1.12	Br	H	CH3	H	H	H	H	H	CH3
1.13	Cl	H	CH3	H	H	H	H	H	CH3
1.14	I	H	CH3	H	H	H	H	H	CH3
1.15	CN	H	CH3	H	H	H	H	H	H
1.16	CF3	H	CH3	H	H	H	H	H	H
1.17	Br	H	CH3	H	H	H	H	H	H
1.18	Cl	H	CH3	H	H	H	H	H	H
1.19	I	H	CH3	H	H	H	H	H	H
1.20	CN	H	H	H	H	H	H	H	CH2Ph
1.21	CF3	H	H	H	H	H	H	H	CH2Ph
1.22	Br	H	H	H	H	H	H	H	CH2Ph
1.23	Cl	H	H	H	H	H	H	H	CH2Ph
1.24	I	H	H	H	H	H	H	H	CH2Ph
1.25	CN	H	CH3	H	H	H	H	H	CH2Ph
1.26	CF3	H	CH3	H	H	H	H	H	CH2Ph
1.27	Br	H	CH3	H	H	H	H	H	CH2Ph
1.28	Cl	H	CH3	H	H	H	H	H	CH2Ph
1.29	I	H	CH3	H	H	H	H	H	CH2Ph
1.30	CH3S	H	H	H	H	H	H	H	CH3
1.31	CH3S	H	H	H	H	H	H	H	H
1.32	CH3S	H	H	H	H	H	H	H	CH2Ph
1.33	CH3S	H	CH3	H	H	H	H	H	CH3
1.34	CH3S	H	CH3	H	H	H	H	H	H
1.35	CH3S	H	CH3	H	H	H	H	H	CH2Ph
1.36	C(O)H	H	H	H	H	H	H	H	CH3
1.37	C(O)H	H	H	H	H	H	H	H	H
1.38	C(O)H	H	H	H	H	H	H	H	CH2Ph
1.39	C(O)H	H	CH3	H	H	H	H	H	CH3
1.40	C(O)H	H	CH3	H	H	H	H	H	H
1.41	C(O)H	H	CH3	H	H	H	H	H	CH2Ph
1.42	CHCH2	H	H	H	H	H	H	H	CH3
1.43	CHCH2	H	H	H	H	H	H	H	H
1.44	CHCH2	H	H	H	H	H	H	H	CH2Ph
1.45	CHCH2	H	CH3	H	H	H	H	H	CH3
1.46	CHCH2	H	CH3	H	H	H	H	H	H
1.47	CHCH2	H	CH3	H	H	H	H	H	CH2Ph
1.48	CHF2	H	H	H	H	H	H	H	CH3
1.49	CHF2	H	H	H	H	H	H	H	H
1.50	CHF2	H	H	H	H	H	H	H	CH2Ph
1.51	CHF2	H	CH3	H	H	H	H	H	CH3
1.52	CHF2	H	CH3	H	H	H	H	H	H
1.53	CHF2	H	CH3	H	H	H	H	H	CH2Ph

[0028] Table 2 below includes examples of compounds of formula (Ib) wherein W is O and R₁, R₂, R₃, R₅, R₆, R₇, R₈ and X are as defined.

Table 2

Compound	X	R1	R2	R3	R5	R6	R7	R8
2.00	CN	H	H	H	H	H	H	H
2.01	CF3	H	H	H	H	H	H	H
2.02	Br	H	H	H	H	H	H	H
2.03	Cl	H	H	H	H	H	H	H
2.04	I	H	H	H	H	H	H	H
2.05	CN	H	CH3	H	H	H	H	H
2.06	CF3	H	CH3	H	H	H	H	H
2.07	Br	H	CH3	H	H	H	H	H
2.08	Cl	H	CH3	H	H	H	H	H
2.09	I	H	CH3	H	H	H	H	H
2.10	CH3S	H	H	H	H	H	H	H
2.11	CH3S	H	CH3	H	H	H	H	H
2.12	CHCH2	H	H	H	H	H	H	H
2.13	CHCH2	H	CH3	H	H	H	H	H
2.14	CHF2	H	H	H	H	H	H	H
2.15	CHF2	H	CH3	H	H	H	H	H
2.16	C(O)H	H	H	H	H	H	H	H
2.17	C(O)H	H	CH3	H	H	H	H	H

[0029] The compounds of Formula I according to the invention can be used as plant growth regulators or seed germination promoters by themselves, but they are generally formulated into plant growth regulation or seed germination promotion compositions using formulation adjuvants, such as carriers, solvents and surface-active agents (SFAs). Thus, the present invention further provides a plant growth regulator composition comprising a plant growth regulation compound as described herein and an agriculturally acceptable formulation adjuvant or carrier. The present invention further provides a seed germination promoter composition comprising a seed germination promoter compound as described herein and an agriculturally acceptable formulation adjuvant or carrier. Preferably the composition consists essentially of a compound of Formula I and an agriculturally acceptable formulation adjuvant or carrier. In the alternative, the composition consists of a compound of Formula I and at least one agriculturally acceptable formulation adjuvant or carrier.

[0030] In one embodiment, the present invention provides a composition comprising a compound of Formula I and an agriculturally acceptable carrier, wherein in Formula I, W is O; Q is formula (I'); R1 is H, trifluoromethyl, cyano, halogen or methyl; R₂ is H, methoxy, trifluoromethyl, cyano, halogen or methyl; X is halogen, C₁-C₆haloalkyl or cyano; R₃ is H or C₁-C₆alkyl; R₅, R₆, R₇ and R₈ are independently hydrogen or methyl; R₉ is hydrogen, C₁-C₆alkyl, C₁-C₆haloalkyl, C₂-C₆ alkenyl, C₂-C₆alkynyl, or R₉ is C₁-C₆ alkyl substituted by at least one C₁-C₆alkoxy, C₁-C₆alkylthio, phenyl.

[0031] In a further embodiment, the present invention provides a composition comprising a compound of Formula I and an agriculturally acceptable carrier, wherein in Formula I, W is O; Q is formula (I'); R₁ is H; R₂ is H or methyl; X is Cl, BR, I, or trifluoromethyl or cyano; R₃ is H; R₅, R₆, R₇ and R₈ are hydrogen; R₉ is hydrogen or methyl.

[0032] In another embodiment, the present invention provides a composition comprising a compound of Formula I and an agriculturally acceptable carrier, wherein in Formula I, W is O; Q is formula (I"); R1 is H, trifluoromethyl, cyano, halogen or methyl; R₂ is H, methoxy, trifluoromethyl, cyano, halogen or methyl; X is halogen, C₁-C₆haloalkyl or cyano; R₅, R₆, R₇ and R₈ are independently hydrogen or methyl.

[0033] In a further embodiment, the present invention provides a composition comprising a compound of Formula I and an agriculturally acceptable carrier, wherein in Formula I, W is O; Q is formula (II'); R₁ is H; R₂ is H or methyl; X is Cl, BR, I, or trifluoromethyl or cyano; R₅, R₆, R₇ and R₈ are hydrogen.

[0034] The composition can be in the form of concentrates which are diluted prior to use, although ready-to-use compositions can also be made. The final dilution is usually made with water, but can be made instead of, or in addition to, water, with, for example, liquid fertilisers, micronutrients, biological organisms, oil or solvents.

[0035] The compositions generally comprise from 0.1 to 99 % by weight, especially from 0.1 to 95 % by weight, compounds of Formula I and from 1 to 99.9 % by weight of a formulation adjuvant which preferably includes from 0 to 25 % by weight of a surface-active substance.

[0036] The compositions can be chosen from a number of formulation types, many of which are known from the Manual on Development and Use of FAO Specifications for Plant Protection Products, 5th Edition, 1999. These include dustable powders (DP), soluble powders (SP), water soluble granules (SG), water dispersible granules (WG), wettable powders (WP), granules (GR) (slow or fast release), soluble concentrates (SL), oil miscible liquids (OL), ultra low volume liquids (UL), emulsifiable concentrates (EC), dispersible concentrates (DC), emulsions (both oil in water (EW) and water in oil (EO)), microemulsions (ME), suspension concentrates (SC), aerosols, capsule suspensions (CS) and seed treatment formulations. The formulation type chosen in any instance will depend upon the particular purpose envisaged and the physical, chemical and biological properties of the compound of Formula (I).

[0037] Dustable powders (DP) may be prepared by mixing a compound of Formula (I) with one or more solid diluents (for example natural clays, kaolin, pyrophyllite, bentonite, alumina, montmorillonite, kieselguhr, chalk, diatomaceous earths, calcium phosphates, calcium and magnesium carbonates, sulphur, lime, flours, talc and other organic and inorganic solid carriers) and mechanically grinding the mixture to a fine powder.

[0038] Soluble powders (SP) may be prepared by mixing a compound of Formula (I) with one or more water-soluble inorganic salts (such as sodium bicarbonate, sodium carbonate or magnesium sulphate) or one or more water-soluble organic solids (such as a polysaccharide) and, optionally, one or more wetting agents, one or more dispersing agents or a mixture of said agents to improve water dispersibility/solubility. The mixture is then ground to a fine powder. Similar compositions may also be granulated to form water soluble granules (SG).

[0039] Wettable powders (WP) may be prepared by mixing a compound of Formula (I) with one or more solid diluents or carriers, one or more wetting agents and, preferably, one or more dispersing agents and, optionally, one or more suspending agents to facilitate the dispersion in liquids. The mixture is then ground to a fine powder. Similar compositions may also be granulated to form water dispersible granules (WG).

[0040] Granules (GR) may be formed either by granulating a mixture of a compound of Formula (I) and one or more powdered solid diluents or carriers, or from pre-formed blank granules by absorbing a compound of Formula (I) (or a solution thereof, in a suitable agent) in a porous granular material (such as pumice, attapulgite clays, fuller's earth, kieselguhr, diatomaceous earths or ground corn cobs) or by adsorbing a compound of Formula (I) (or a solution thereof, in a suitable agent) on to a hard core material (such as sands, silicates, mineral carbonates, sulphates or phosphates) and drying if necessary. Agents which are commonly used to aid absorption or adsorption include solvents (such as aliphatic and aromatic petroleum solvents, alcohols, ethers, ketones and esters) and sticking agents (such as polyvinyl acetates, polyvinyl alcohols, dextrins, sugars and vegetable oils). One or more other additives may also be included in granules (for example an emulsifying agent, wetting agent or dispersing agent).

[0041] Dispersible Concentrates (DC) may be prepared by dissolving a compound of Formula (I) in water or an organic solvent, such as a ketone, alcohol or glycol ether. These solutions may contain a surface active agent (for example to improve water dilution or prevent crystallisation in a spray tank).

[0042] Emulsifiable concentrates (EC) or oil-in-water emulsions (EW) may be prepared by dissolving a compound of Formula (I) in an organic solvent (optionally containing one or more wetting agents, one or more emulsifying agents or a mixture of said agents). Suitable organic solvents for use in ECs include aromatic hydrocarbons (such as alkylbenzenes or alkylnaphthalenes, exemplified by SOLVESSO 100, SOLVESSO 150 and SOLVESSO 200; SOLVESSO is a Registered Trade Mark), ketones (such as cyclohexanone or methylcyclohexanone) and alcohols (such as benzyl alcohol, furfuryl alcohol or butanol), N-alkylpyrrolidones (such as N-methylpyrrolidone or N-octylpyrrolidone), dimethyl amides of fatty acids (such as C₈-C₁₀ fatty acid dimethylamide) and chlorinated hydrocarbons. An EC product may spontaneously emulsify on addition to water, to produce an emulsion with sufficient stability to allow spray application through appropriate equipment.

[0043] Preparation of an EW involves obtaining a compound of Formula (I) either as a liquid (if it is not a liquid at room temperature, it may be melted at a reasonable temperature, typically below 70°C) or in solution (by dissolving it in an appropriate solvent) and then emulsifying the resultant liquid or solution into water containing one or more SFAs, under high shear, to produce an emulsion. Suitable solvents for use in EWs include vegetable oils, chlorinated hydrocarbons (such as chlorobenzenes), aromatic solvents (such as alkylbenzenes or alkylnaphthalenes) and other appropriate organic solvents which have a low solubility in water.

[0044] Microemulsions (ME) may be prepared by mixing water with a blend of one or more solvents with one or more SFAs, to produce spontaneously a thermodynamically stable isotropic liquid formulation. A compound of Formula (I) is present initially in either the water or the solvent/SFA blend. Suitable solvents for use in MEs include those hereinbefore described for use in ECs or in EWs. An ME may be either an oil-in-water or a water-in-oil system (which system is present may be determined by conductivity measurements) and may be suitable for mixing water-soluble and oil-soluble pesticides in the same formulation. An ME is suitable for dilution into water, either remaining as a microemulsion or forming a conventional oil-in-water emulsion.

[0045] Suspension concentrates (SC) may comprise aqueous or non-aqueous suspensions of finely divided insoluble solid particles of a compound of Formula (I). SCs may be prepared by ball or bead milling the solid compound of Formula (I) in a suitable medium, optionally with one or more dispersing agents, to produce a fine particle suspension of the compound. One or more wetting agents may be included in the composition and a suspending agent may be included to reduce the rate at which the particles settle. Alternatively, a compound of Formula (I) may be dry milled and added to water, containing agents hereinbefore described, to produce the desired end product.

[0046] Aerosol formulations comprise a compound of Formula (I) and a suitable propellant (for example n-butane). A compound of Formula (I) may also be dissolved or dispersed in a suitable medium (for example water or a water miscible liquid, such as n-propanol) to provide compositions for use in non-pressurised, hand-actuated spray pumps.

[0047] Capsule suspensions (CS) may be prepared in a manner similar to the preparation of EW formulations but with an additional polymerisation stage such that an aqueous dispersion of oil droplets is obtained, in which each oil droplet is encapsulated by a polymeric shell and contains a compound of Formula (I) and, optionally, a carrier or diluent therefor. The polymeric shell may be produced by either an interfacial polycondensation reaction or by a coacervation procedure. The compositions may provide for controlled release of the compound of Formula (I) and they may be used for seed treatment. A compound of Formula (I) may also be formulated in a biodegradable polymeric matrix to provide a slow, controlled release of the compound.

[0048] The composition may include one or more additives to improve the biological performance of the composition, for example by improving wetting, retention or distribution on surfaces; resistance to rain on treated surfaces; or uptake or mobility of a compound of Formula (I). Such additives include surface active agents (SFAs), spray additives based on oils, for example certain mineral oils or natural plant oils (such as soy bean and rape seed oil), and blends of these with other bio-enhancing adjuvants (ingredients which may aid or modify the action of a compound of Formula (I)).

[0049] Wetting agents, dispersing agents and emulsifying agents may be SFAs of the cationic, anionic, amphoteric or non-ionic type.

[0050] Suitable SFAs of the cationic type include quaternary ammonium compounds (for example cetyltrimethyl ammonium bromide), imidazolines and amine salts.

[0051] Suitable anionic SFAs include alkali metals salts of fatty acids, salts of aliphatic monoesters of sulphuric acid (for example sodium lauryl sulphate), salts of sulphonated aromatic compounds (for example sodium dodecylbenzenesulphonate, calcium dodecylbenzenesulphonate, butylnaphthalene sulphonate and mixtures of sodium diisopropyl- and tri-isopropyl-naphthalene sulphonates), ether sulphates, alcohol ether sulphates (for example sodium laureth-3-sulphate), ether carboxylates (for example sodium laureth-3-carboxylate), phosphate esters (products from the reaction between one or more fatty alcohols and phosphoric acid (predominately mono-esters) or phosphorus pentoxide (predominately diesters), for example the reaction between lauryl alcohol and tetraphosphoric acid; additionally these products may be ethoxylated), sulphosuccinamates, paraffin or olefine sulphonates, taurates and lignosulphonates.

[0052] Suitable SFAs of the amphoteric type include betaines, propionates and glycinates.

[0053] Suitable SFAs of the non-ionic type include condensation products of alkylene oxides, such as ethylene oxide, propylene oxide, butylene oxide or mixtures thereof, with fatty alcohols (such as oleyl alcohol or cetyl alcohol) or with alkylphenols (such as octylphenol, nonylphenol or octylcresol); partial esters derived from long chain fatty acids or hexitol anhydrides; condensation products of said partial esters with ethylene oxide; block polymers (comprising ethylene oxide and propylene oxide); alkanolamides; simple esters (for example fatty acid polyethylene glycol esters); amine oxides (for example lauryl dimethyl amine oxide); and lecithins.

[0054] Suitable suspending agents include hydrophilic colloids (such as polysaccharides, polyvinylpyrrolidone or sodium carboxymethylcellulose) and swelling clays (such as bentonite or attapulgite).

[0055] The present invention still further provides a method for regulating the growth of plants in a locus, wherein the method comprises application to the locus of a plant growth regulating amount of a composition according to the present invention. Preferably the composition is applied by spray application to the leaves of the plant.

[0056] The present invention also provides a method for promoting the germination of seeds, comprising applying to the seeds, or to a locus containing seeds, a seed germination promoting amount of a composition according to the present invention.

[0057] The application is generally made by spraying the composition, typically by tractor mounted sprayer for large areas, but other methods such as dusting (for powders), drip or drench can also be used. Alternatively the composition may be applied in furrow or directly to a seed before or at the time of planting.

[0058] The compound of formula (I) or composition of the present invention may be applied to a plant, part of the plant, plant organ, plant propagation material or a surrounding area thereof.

[0059] In one embodiment, the invention relates to a method of treating a plant propagation material comprising applying to the plant propagation material a composition of the present invention in an amount effective to promote germination and/or regulate plant growth. The invention also relates to a plant propagation material treated with a compound of formula (I) or a composition of the present invention. Preferably, the plant propagation material is a seed.

[0060] The term "plant propagation material" denotes all the generative parts of the plant, such as seeds, which can be used for the multiplication of the latter and vegetative plant materials such as cuttings and tubers. In particular, there may be mentioned the seeds, roots, fruits, tubers, bulbs, and rhizomes.

[0061] Methods for applying active ingredients to plant propagation material, especially seeds, are known in the art, and include dressing, coating, pelleting and soaking application methods of the propagation material. The treatment can be applied to the seed at any time between harvest of the seed and sowing of the seed or during the sowing process. The seed may also be primed either before or after the treatment. The compound of formula (I) may optionally be applied in combination with a controlled release coating or technology so that the compound is released over time.

[0062] The composition of the present invention may be applied pre-emergence or post-emergence. Suitably, where the composition is being used to regulate the growth of crop plants, it may be applied pre or post-emergence, but preferably post-emergence of the crop. Where the composition is used to promote the germination of seeds, it may be applied pre-emergence.

[0063] The rates of application of compounds of Formula I may vary within wide limits and depend on the nature of the soil, the method of application (pre- or post-emergence; seed dressing; application to the seed furrow; no tillage application etc.), the crop plant, the prevailing climatic conditions, and other factors governed by the method of application, the time of application and the target crop. For foliar or drench application, the compounds of Formula I according to the invention are generally applied at a rate of from 0.001 to 2000 g/ha, especially from 0.001 to 400 g/ha. For seed treatment the rate of application is generally between 0.0005 and 150g per 100kg of seed.

[0064] Plants in which the composition according to the invention can be used include crops such as cereals (for example wheat, barley, rye, oats); beet (for example sugar beet or fodder beet); fruits (for example pomes, stone fruits or soft fruits, such as apples, pears, plums, peaches, almonds, cherries, strawberries, raspberries or blackberries); leguminous plants (for example beans, lentils, peas or soybeans); oil plants (for example rape, mustard, poppy, olives, sunflowers, coconut, castor oil plants, cocoa beans or groundnuts); cucumber plants (for example marrows, cucumbers or melons); fibre plants (for example cotton, flax, hemp or jute); citrus fruit (for example oranges, lemons, grapefruit or mandarins); vegetables (for example spinach, lettuce, asparagus, cabbages, carrots, onions, tomatoes, potatoes, cucurbits or paprika); lauraceae (for example avocados, cinnamon or camphor); maize; rice; tobacco; nuts; coffee; sugar cane; tea; vines; hops; durian; bananas; natural rubber plants; turf or ornamentals (for example flowers, shrubs, broad-leaved trees or evergreens such as conifers). This list does not represent any limitation.

[0065] The invention may also be used to regulate the growth, or promote the germination of seeds of non-crop plants, for example to facilitate weed control by synchronizing germination.

[0066] Crops are to be understood as also including those crops which have been modified by conventional methods of breeding or by genetic engineering. For example, the invention may be used in conjunction with crops that have been rendered tolerant to herbicides or classes of herbicides (e.g. ALS-, GS-, EPSPS-, PPO-, ACCase- and HPPD-inhibitors). An example of a crop that has been rendered tolerant to imidazolinones, e.g. imazamox, by conventional methods of breeding is Clearfield® summer rape (canola). Examples of crops that have been rendered tolerant to herbicides by genetic engineering methods include e.g. glyphosate- and glufosinate-resistant maize varieties commercially available under the trade names RoundupReady® and LibertyLink®. Methods of rending crop plants tolerant to HPPD-inhibitors are known, for example from WO0246387; for example the crop plant is transgenic in respect of a polynucleotide comprising a DNA sequence which encodes an HPPD-inhibitor resistant HPPD enzyme derived from a bacterium, more particularly from Pseudomonas fluorescens or Shewanella colwelliana, or from a plant, more particularly, derived from a monocot plant or, yet more particularly, from a barley, maize, wheat, rice, Brachiaria, Chenchrus, Lolium, Festuca, Setaria, Eleusine, Sorghum or Avena species.

[0067] Crops are also to be understood as being those which have been rendered resistant to harmful insects by genetic engineering methods, for example Bt maize (resistant to European corn borer), Bt cotton (resistant to cotton boll weevil) and also Bt potatoes (resistant to Colorado beetle). Examples of Bt maize are the Bt 176 maize hybrids of NK® (Syngenta Seeds). The Bt toxin is a protein that is formed naturally by Bacillus thuringiensis soil bacteria. Examples of toxins, or transgenic plants able to synthesise such toxins, are described in EP-A-451 878, EP-A-374 753, WO 93/07278, WO 95/34656, WO 03/052073 and EP-A-427 529. Examples of transgenic plants comprising one or more genes that code for an insecticidal resistance and express one or more toxins are KnockOut® (maize), Yield Gard® (maize), NuCOTIN33B® (cotton), Bollgard® (cotton), NewLeaf® (potatoes), NatureGard® and Protexcta®. Plant crops or seed material thereof can be both resistant to herbicides and, at the same time, resistant to insect feeding ("stacked" transgenic events). For example, seed can have the ability to express an insecticidal Cry3 protein while at the same time being tolerant to glyphosate.

[0068] Crops are also to be understood to include those which are obtained by conventional methods of breeding or genetic engineering and contain so-called output traits (e.g. improved storage stability, higher nutritional value and improved flavour).

[0069] Compounds of the present invention may be in the form of an ester or an acid, either of which may have plant growth regulating properties. As suggested in WO2009/109570, it is thought that the ester form of the compounds of Formula I may be hydrolysed in planta to the acid form. This may be a particular advantage where the esterified compounds are more readily taken up by the plant, for example through leaf tissue.

[0070] Compounds and compositions of the present invention may be applied in combination with other active ingredients or products for use in agriculture, including insecticides, fungicides, herbicides, plant growth regulators, crop enhancing compounds, nutrients and biologicals. Examples of suitable mixing partners may be found in the Pesticide Manual, 15th edition (published by the British Crop Protection Council). Such mixtures may be applied to a plant, plant propagation material or plant growing locus either simultaneously (for example as a pre-formulated mixture or a tank mix), or sequentially in a suitable timescale. Co-application of pesticides with the present invention has the added benefit of minimising farmer time spent applying products to crops. In a further aspect of the present invention, the compounds or composition of the present invention may be applied in combination with one or more other compounds having a crop enhancement effect. Such compounds include micronutrients, saccharides, amino acids, flavonoids, quinines, and plant activators / growth stimulators. For example, such compounds include natural or synthetic hormones, auxins, brassinosteroids, gibberellins, abscisic acid, cytokinins, jasmonates, strigolactones, salicylic acid, ethylene, 1-methylcyclopropene, trinexapac-ethyl or derivatives thereof. Such compounds also include pesticides that have a crop enhancement effect, for example strobilurins (including azoxystrobin, pyraclostrobin), and neonicotinoids (including thiamethoxam, and imidacloprid).

[0071] The compounds according to the invention or a composition, comprising a compound according to the invention, can also be used as herbicides. The invention thus also covers a method for killing weeds and unwanted vegetation, wherein the method comprises applying to said weeds or unwanted vegetation an amount of a compound or a composition according to the invention. The invention thus also covers a method for controlling weeds comprising applying to weeds post-emergence an effective amount of a compound or a composition according to the invention. The invention thus also covers a method for controlling weeds comprising applying to the soil before said weeds emerge an effective amount of a compound or a composition according to the invention.

[0072] The compounds of the invention may be made by the following methods.

[0073] Compounds of formula (Ia) may be prepared from a compound of formula (III) via acylation by reaction of a compounds of formula (II) wherein Z is a halogen such as chlorine, such reactions are usually carried out in the presence of a base, and optionally in the presence of a nucleophilic catalyst. Alternatively, it is possible to conduct the reaction in a biphasic system comprising an organic solvent, preferably ethyl acetate, and an aqueous solvent, preferably a solution of sodium hydrogen carbonate.

[0074] Compounds of formula (II) are commercially available, such as methyl succinate chloride or can be made by methods known to a person skilled in the art.

[0075] Compounds of formula (Ic) may be made by treatment of compounds of formula (Ia), wherein R₉ is not hydrogen, by hydrolysis of the ester group under standard conditions, such as treatment with an alkali hydroxide, such as sodium hydroxide or potassium hydroxide, in a solvent, such as ethanol or tetrahydrofuran, in the presence of water. Another alternative is the treatment of the ester of formula (Ia) with an acid, such as trifluoroacetic acid, in a solvent, such as dichloromethane, followed by addition of water. The reaction is carried out preferably at a temperature of from -20°C to +100°C, more preferably from 20°C to 80°C, in particular at 50°C.

[0076] Compounds of formula (Ia) (wherein R₉ is not hydrogen) may be prepared from a compound of formula (Ic) via esterification by reaction of an alcohol derivative in the presence of a coupling reagent, such as DCC (N,N'-dicyclohexylcarbodiimide), EDC (1-ethyl-3-[3-dimethylamino-propyl]carbodiimide hydrochloride) or BOP-Cl (bis(2-oxo-3-oxazolidinyl)phosphonic chloride), in the presence of a base, such as pyridine, triethylamine, 4-(dimethylamino)pyridine or diisopropylethylamine, and optionally in the presence of a nucleophilic catalyst, such as hydroxybenzotriazole.

[0077] Alternatively, Compounds of formula (Ia) may be prepared from a compound of formula (Id), wherein Z is a leaving group such as chlorine, via acylation. The acylation reaction may be carried out under basic conditions (for example in the presence of pyridine, triethylamine, 4-(dimethylamino)pyridine or diisopropylethylamine) and in a suitable solvent, such as, for instance, tetrahydrofuran, optionally in the presence of a nucleophilic catalyst. The reaction is carried out at a temperature of from -120°C to +130°C, preferably from -100°C to 100°C. Alternatively, the reaction may be conducted in a biphasic system comprising an organic solvent, preferably ethyl acetate, and an aqueous solvent, preferably a saturated solution of sodium bicarbonate.

[0078] Compounds of formula (Id) may be prepared from a compound of formula (Ic), under standard conditions, such as treatment with thionyl chloride or oxalyl chloride, in a solvent, such as dichloromethane. The reaction is carried out preferably at a temperature of from - 20°C to +100°C, more preferably from 0°C to 50°C, in particular at ambient temperature.

[0079] Compounds of formula (Ic) may be made by treatment of compounds of formula (III) by treatment with an anhydride derivative of formula (IV), such as succinyl anhydride, in a solvent, such as tetrahydrofuran. The reaction is carried out preferably at a temperature from - 20°C to +120°C, more preferably from 20°C to 120°C.

[0080] Compounds of Formula (Ia) wherein X is selected from aryl, heteroaryl or C₃-C₈cycloalkyl derivatives such as thiophen, vinyl, allyl or cyclopropyl can be prepared by the reaction of compounds of formula (Ie), wherein LG is a suitable leaving group, such as halogen or triflate, with a derivative of formula Z'-X, wherein Z' is a boron or a tin derivative and X is as described for the compound of Formula (Ia), in the presence of a suitable catalyst/ligand system, often a palladium (0) complex and optionally in the presence of a base such as potassium carbonate. These reactions can be carried out optionally under microwave irradiation. These reactions being known to the person skilled in the art under the name of Stille, Suzuki coupling, see for example: Strategic Applications of Named Reactions in Organic Synthesis Kurti, Laszlo; Czako, Barbara; Editors. USA. (2005), Publisher: Elsevier Academic Press, Burlington, Mass. p.448 (Suzuki coupling) and p.438 (Stille coupling) and cited references.

[0081] Compounds of Formula (Ia) wherein X is CCR where R is an C₁-C₆ alkyl, H or trialkyl silyl can be prepared by the reaction of compounds of formula (Ie), wherein LG is a suitable leaving group such as for example halogen or triflate, with a derivative of formula HCCR in the presence of a suitable catalyst/ligand system, for example a palladium (0) complex with or without a source of copper such as copper iodide and an organic base such as diisopropylethyl amine. The general reaction type is known to the person skilled in the art under the name of Sonogashira coupling, see for example: Strategic Applications of Named Reactions in Organic Synthesis Kurti, Laszlo; Czako, Barbara; Editors. USA. (2005), Publisher: Elsevier Academic Press, Burlington, Mass. p.424 (Sonogashira coupling) and cited references. Compounds of Formula (Ia) wherein X is CCH can be prepared by the reaction of compounds of formula (Ia) type wherein X is CCSiR₃ where R is a C1-C6 alkyl group by reaction with a base such as potassium carbonate of a fluoride source such as potassium fluoride.

[0082] Compounds of Formula (Ib) may be prepared, in one step from a compound of Formula (III) by reaction in the presence of compound of Formula (II) by heating, optionally in the presence of an acid, such as acetic acid or a base, such as triethylamine. These reaction types are well known by a person skilled in the art. A few literature examples: Journal of Fluorine Chemistry (2006), 127(3), 417-425 or Tetrahedron Letters (2005), 46(5), 759-762. Alternatively, compounds of Formula (Ib) may be prepared, in one step from a compound of Formula (III) by reaction in the presence of compound of Formula (IV) by heating, optionally in the presence of an acid, such as acetic acid or a base, such as triethylamine.These reaction types are well known by a person skilled in the art. A few literature examples: Organic Letters (2011), 13(16), 4320-4323, Pharma Chemica (2011), 3(2), 283-286, Journal of Medicinal Chemistry (2007), 50(6), 1124-1132, Journal of the American Chemical Society (2006), 128(14), 4892-4901 or European Journal of Medicinal Chemistry (2011), 46(9), 4324-4329.

[0083] Compounds of Formula (Ib) may be prepared from a compound of Formula (Ic) by reaction in the presence of a coupling reagent, such as diimidazolyl ketone, DCC (N,N'-dicyclohexylcarbodiimide), EDCI (1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide monohydrochloride) or BOP-Cl (bis(2-oxo-3-oxazolidinyl)phosphonic chloride), optionally in the presence of a base, such as pyridine, triethylamine, 4-(dimethylamino)pyridine or diisopropylethylamine, and optionally in the presence of a nucleophilic catalyst, such as hydroxybenzotriazole. Alternatively, compounds of Formula (Ib) may be prepared from a compound of Formula (Ic) by reaction in the presence of anhydride or acid chloride derivatives, such as acetic anhydride, optionally in the presence of a base such as sodium acetate.

[0084] Alternatively, compounds of Formula (Ib) may be prepared from a compound of Formula (Ic) via acid halides of formula (Id), wherein Z is a leaving group such as chlorine by reaction of compound (Ic) under standard conditions, such as treatment with thionyl chloride or oxalyl chloride.

[0085] Compounds of Formula (Ib) may be prepared from a compound of Formula (Ia), when R₉ is hydrogen or alkyl substituted, such as methyl, by heating in presence of an acid or a base, such as hydrogen chloride or cesium carbonate and, optionally in the presence of a nucleophilic catalyst such as potassium iodide.

[0086] Compounds of Formula (If) wherein W is O may be prepared from a compound of Formula (Ia) wherein W are oxygen, by treatment with a thio-transfer reagent, such as Lawesson's reagent or phosphorus pentasulfide.

[0087] Compounds of Formula (If) wherein W is S may be prepared from a compound of Formula (Ia) wherein W are oxygen, by treatment with a thio-transfer reagent, such as Lawesson's reagent or phosphorus pentasulfide.

[0088] Compounds of Formula (Ig) wherein W is O may be prepared from a compound of Formula (Ib) wherein W are oxygen, by treatment with a thio-transfer reagent, such as Lawesson's reagent or phosphorus pentasulfide.

[0089] Compounds of Formula (Ig) wherein W is S may be prepared from a compound of Formula (Ib) wherein W are oxygen, by treatment with a thio-transfer reagent, such as Lawesson's reagent or phosphorus pentasulfide.

[0090] Alternatively, compounds of Formula (Ia) may be prepared from a compound of Formula (Id) where in R'₉ is a alkyl derivative such as methyl via transesterification in presence of a alcohol derivative (R₉OH). Transesterification reactions are well known to a person skilled in the art and where reviewed, for example, in "Synthetic Organic Methodology: Comprehensive Organic Transformations. A Guide to Functional Group Preparations." Larock, R. C. 1989, p. 985-987, Publisher: (VCH, Weinheim, Fed. Rep. Ger.) or March's Advanced Organic Chemistry: Reactions, Mechanisms, and Structure, 5th Edition, Smith, Michael B.; March, Jerry.UK. 2000, Publisher: (John Wiley & Sons, Ltd., Chichester, UK) p 486-487.

[0091] Compounds of Formula (II), (III) and (IV) are either known or may be made by methods known to a person skilled in the art or / and are commercialy available.

EXAMPLES

[0092] The following HPLC-MS methods were used for the analysis of the compounds:

Method A: Standard

[0093] Spectra were recorded on a Mass Spectrometer from Waters (SQD or ZQ Single quadrupole mass spectrometer) equipped with an electrospray source (Polarity: positive or negative ions, Capillary: 3.00 kV, Cone range: 30-60 V, Extractor: 2.00 V, Source Temperature: 150°C, Desolvation Temperature: 350°C, Cone Gas Flow: 50 L/Hr, Desolvation Gas Flow: 650 L/Hr, Mass range: 100 to 900 Da) and an Acquity UPLC from Waters: Binary pump, heated column compartment and diode-array detector. Solvent degasser, binary pump, heated column compartment and diode-array detector. Column: Waters UPLC HSS T3 , 1.8 µm, 30 x 2.1 mm, Temp: 60 °C, DAD Wavelength range (nm): 210 to 400, Solvent Gradient: A = water + 5% MeOH + 0.05 % HCOOH, B= Acetonitrile + 0.05 % HCOOH: gradient: gradient: 0.0-0.2min (10%B); 0.2-1.2min(10%-100%B); 1.2-1.4min(100%B); 1.4-1.45min(100%-10%B); Flow (ml/min) 0.85.

[0094] The following abbreviations are used throughout this section: s = singlet; bs = broad singlet; d = doublet; dd = double doublet; dt = double triplet; t = triplet, tt = triple triplet, q = quartet, m = multiplet; Me = methyl; Et = ethyl; Pr = propyl; Bu = butyl; M.p. = melting point; RT = retention time, M+H⁺ = molecular cation (i.e. measured molecular weight).

Example I: Preparation of methyl 4-[(4-chloro-2-pyridyl)amino]-4-oxo-butanoate (A1)

[0095] 

[0096] The 4-chloropyridin-2-amine (commercially available, 1 g, 7.78 mmol) was dissolved in tetrahydrofuran (16 mL) then N,N-dimethylaniline (0.95 g, 0.996 mL, 7.78 mmol) and methyl-4-chloro-4-oxo-butanoate (1.33 g, 1.1 mL, 8.56 mmol) were successively added. The mixture was refluxed for 12 h. The reaction was stopped and the solution was partitioned between ethyl acetate and water. The aqueous layer was separated and extracted with ethyl acetate (2x). The combined organic layer was dried on magnesium sulfate and concentrated under vacuum. The residue was purified by flash chromatography eluting with cyclohexane-ethyl acetate (3/1) to give methyl 4-[(4-chloro-2-pyridyl)amino]-4-oxo-butanoate A1 (69%). M.p. = 113-114 °C. ¹H NMR (400 MHz, CDCl₃) δ 8.37 (sb, 1H), 8.28 (s, 1H), 8.16 (d, 1H), 7.04 (d, 1H), 3.72 (s, 3H), 2.74 (m, 4H) ppm. LC-MS (Method A): RT 0.74, 243 (M+H⁺)

[0097] The compounds A2, A3, A4, A5 and A11 from table A were prepared by the same method using the appropriate starting material. The compounds A6 and A9 from table A were prepared by the same method using the appropriate starting material and in these cases, A1 was isolated too as a by-product via halogen exchange.

Example II: Preparation of 1-[4-(trifluoromethyl)-2-pyridyl]pyrrolidine-2,5-dione B1

[0098] 

[0099] To a solution of 4-(trifluoromethyl)pyridin-2-amine (485 mg, 2.99 mmol) in xylene (10 mL), in a sealed vial was added dihydro-2,5-furandione (2 equiv., 5.98 mmol). The reaction mixture was stirred at 140°C for 16 h. The solvent was removed by evaporation under vacuum. Then, the residue was dissolved in ethyl acetate and washed with a saturated solution of sodium hydrogenocarbonate, a solution of hydrogen chloride and finally with water. The organic phases were dried over sodium sulfate and concentrated to give the desired compound B1 in 87% yield. LC-MS (Method: A) RT 0.64 (245, M+H⁺). ¹H NMR (400 MHz, CDCl₃): 8.85 (d, 1H), 7.62 (d, 1H), 7.58 (s, 1H), 2.96 (s, 4H) ppm.

Example III: Preparation of 4-[(4-cyano-2-pyridyl)amino]-4-oxo-butanoic acid A7

[0100] 

[0101] Lithium hydroxide (6.89 mmol, 1.05 eq.) was added at ambient temperature to a solution of methyl 4-[(4-cyano-2-pyridyl)amino]-4-oxo-butanoate (Example I, A3, 1.53 g, 6.56 mmol.) in a mixture of tetrahydrofuran (40 ml) and water (20 mL). The reaction mixture was stirred at room temperature for 5 h. The residue was diluted with a saturated solution of sodium hydrogencarbonate and washed with diethyl ether. The aqueous phase was acidified by addition of aqueous hydrochloric acid (concentrated) and extracted two times with diethyl ether. The combined organic layer was dried on magnesium sulfate and concentrated under vacuum to give the desired compound A7 (57%). M.p. = 215-218°C, ¹H NMR (400 MHz, DMSO-d6) δ 12.20 (bs, 1H), 11.01 (s, 1H), 8.56 (d, 1H), 8.85 (s, 1H), 7.52 (d, 1H), 2.78 (m, 2H), 2.55 (m, 2H) ppm. LC-MS (Method A): RT 0.42, 220 (M+H⁺)

[0102] The compounds A8 and A10 from table A were prepared by the same method using the appropriate starting material.

Table A: Compounds of formula (1a) wherein R5, R6, R7 and R8 are H and both W are oxygen

						Analytical data: LCMS, Mp °C or 1H NMR
Compound	X	R1	R2	R3	R9	LCMS method	RT (min.)	Mass
A1 (1.03)	Cl	H	H	H	CH3	A	0.74	243 (M+H+)
A2 (1.01)	CF3	H	H	H	CH3	A	0.83	277 (M+H+)
A3 (1.00)	CN	H	H	H	CH3	A	0.64	234 (M+H+)
A4 (1.13)	Cl	H	CH3	H	CH3	A	0.84	257 (M+H+)
A5	NO2	H	H	H	CH3	A	0.71	254 (M+H+)
A6 (1.04)	I	H	H	H	CH3	A	0.78	335 (M+H+)
A7 (1.05)	CN	H	H	H	H	A	0.42	220 (M+H+)
A8 (1.06)	CF3	H	H	H	H	A	0.70	263 (M+H+)
A9 (1.02)	Br	H	H	H	CH3	1HNMR (400 MHz, CDCl3) 8.46 (s, 1H), 8.23 (sb, 1H), 8.10 (d, 1H), 7.19(d, 1H), 3.72 (s, 3H), 2.74 (m, 4H).
A10 (1.18)	Cl	H	CH3	H	H	A	0.69	243 (M+H+)
A11	OCH 3	H	H	H	CH3	A	0.24	239 (M+H+)

Table B: Compounds of formula (Ib) wherein R5, R6, R7, R8 are H and both W are oxygen,

				Analytical data: LCMS, Mp °C or 1H NMR
Compound	X	R1	R2	LCMS method	RT (min.)	Mass
B1 (2.01)	CF3	H	H	A	0.64	245 (M+H+)

Biological examples

[0103] Two bioassays were developed in order to assay the activity of the compounds of the present invention. In the first assay, the activity of the compound was quantified in beans based on its effect on the elongation of the petiole of the second leaf. In the second assay, the compound's effect on the root growth of wheat was determined.

Example B1: Bean assay

[0104] French beans (Phaseolus vulgaris) of the variety Fulvio were sown in 0.5 litres pots in a sandy loam without additional fertilizer. Plants grew under greenhouse conditions at 22/18°C (day/night) and 80% relative humility; light was supplemented above 25 kLux. Plants were treated with test compounds eleven days after sowing, when the second internode was 2-5 mm long. Before application, the compounds were each dissolved in dimethyl sulfoxide and diluted in a mixture of lanolin-oil and acetone (1:2 ratio by volume). Five micro litres of the test compound was pipetted to the wound that was created after abscising the bract leaf from the base of the second internode. Fourteen days after application, the length of the petiole of the second leaf (measured from the base of the petiole to the base of the first leaflet) was determined in order to quantify the activity of the compounds.

[0105] The following compounds gave at least an increase of 10% of the length of the petiole of the second leaf:

A1, B1

Example B2: Wheat assay

[0106] The test compounds were dissolved in small volumes of dimethyl sulfoxide and diluted to the appropriate concentration with water. Wheat (Triticum aestivum) seeds of the variety Arina were sown in pouches (14.7 × 13.2 cm) containing 10 mL of the appropriate compound solution. The pouches were stored at 17 °C for three days to enable the seeds to germinate. Plants were then stored at 5°C. Twelve days after sowing/application, plants were removed from the pouches and scanned. The effect of the compounds was quantified by determining plant (root and shoot) area and curliness of the roots (curliness is an indicator of brassinosteroid-type activity).

[0107] The following compounds gave at least a reduction of 5% of the plant (root and shoot) area and showed a curly root phenotype:

B1

Example B3: In vitro assay to test for inhibition of plant GSK3/Shaggy-like kinase activity

[0108] Arabidopsis BIN2 kinase (Uniprot Q39011) was produced in E.coli BL21 as an N-terminal hexahistidine fusion protein. In vitro kinase assays were performed by incubating 50 ng His6-BIN2 protein with 5 µg myelin basic protein (Sigma-Aldrich) as substrate and 5 µM ATP as co-substrate in reaction buffer consisting of 40 mM Tris-HCl, 20 mM MgCl₂ and 0.1mg/mL bovine serum albumin in a final reaction volume of 50 µl. Enzyme activity was assessed in the absence and presence of compounds (described in Tables A and B) at 5 µM by measuring the level of ADP produced after incubation for 1 h at 20°C using an enzyme-coupled bioluminescent assay (ADP-Glo, Promega Corp.). The experiment was performed in triplicate.

[0109] The following compounds inhibited the activity of His6-BIN2 by at least 20% relative to the solvent vehicle control:

A1, A2, A3, A5, A6, A7, A8, A9 and B1

Claims

1. A compound of formula (I)

wherein
R₁, R₂ are independently H, C₁-C₆haloalkyl, C₁-C₆alkoxy, cyano, halogen, C₁-C₆alkyl or C₁-C₆alkyl substituted by one or more hydroxyl, amine;
X is halogen, C₁-C₆haloalkyl, cyano, thiocyanate, nitro, amine, C₁-C₆alkoxy, C₁-C₆haloalkoxy, C₁-C₆alkylthio, C₁-C₆haloalkylthio, C₁-C₆alkylsulfinyl, C₁-C₆haloalkylsulfinyl, C₁-C₆alkylsulfonyl, C₁-C₆haloalkylsulfonyl, C₂-C₆alkenyl, C₂-C₆alkynyl, C2-C6 haloalkenyl, C2-C6 haloalkynyl C₁-C₆alkylcarbonyl, C₁-C₆alkoxycarbonyl, C₁-C₆haloalkoxycarbonyl, C₁-C₆haloalkylcarbonyl, C₃-C₈cycloalkyl, formyl, mercapto; or X is heteroaryl or heteroaryl subtituted by one or more halogen, cyano, C₁-C₃alkyl, C₁-C₃haloalkyl;
Or X is an amine group mono- or di-substituted by hydroxyl, C₁-C₆alkyl, C₂-C₆alkenyl, C₂-C₆alkynyl, C₁-C₆haloalkyl, C₁-C₆alkoxy, C₁-C₆haloalkoxy, C₃ to C₈cycloalkyl;
Or X is an amine group mono- or di-substituted by C₁-C₆alkyl substituted by one or more halogen, cyano, nitro, aryl, or aryl subtituted by one or more R10; C₂-C₆alkenyl substituted by one or more R10; or C₂-C₆alkynyl substituted by one or more R10,
Or X is an amine group mono- or di-substituted by heterocyclyl or heterocyclyl subtituted by one or more R10;
Or X is an amine group mono or di-substituted by an aryl or an aryl subtituted by one or more R10;
R₃ is H, C₁-C₆alkyl, C₁-C₆haloalkyl, C₁-C₆alkylcarbonyl, C₁-C₆alkoxycarbonyl; or R₃ is C₁-C₆alkyl substituted by one or more cyano, amine, carbonylamine;
Q is a group according to formula (I')

Or R3 and Q form a cyclic group (I")

wherein,
both W are independently O or S;
R₅, R₆, R₇ and R₈ are independently hydrogen, halogen, nitro, cyano, C₁-C₆alkyl, C₁-C₆haloalkyl, C₁-C₆alkoxy, hydroxyl, -OC(O)R₁₁, amine, N- C₁-C₆alkyl amine, or N,N-di-C₁-C₆ alkyl amine;
R₁₁ is hydrogen, C₁-C₆ alkyl, C₁-C₆ alkoxy, or C₁-C₆ haloalkyl;
R₉ is hydrogen, C₁-C₆ alkyl, C₁-C₆ haloalkyl, C₂-C₆ alkenyl, C₂-C₆ haloalkenyl, C₂-C₆ alkynyl, C₂-C₆ haloalkynyl, C₃-C₇ cycloalkyl, aryl or aryl substituted by one to five substituents R₁₀, heterocyclyl or heterocyclyl substituted by one to five substituents R₁₀;
or R₉ is C₁-C₆ alkyl substituted by one or more cyano, nitro, amine, hydroxyl, C₁-C₆ alkoxy, C₁-C₆ haloalkoxy, C₁-C₆ alkylthio, C₁-C₆ haloalkylthio, C₁-C₆ alkylsulfinyl, C₁-C₆ haloalkylsulfinyl, C₁-C₆ alkylsulfonyl, C₁-C₆ haloalkylsulfonyl, C₃-C₇ cycloalkyl, N-C₁-C₆ alkyl amine, N,N-di-C₁-C₆ alkyl amine, aryl or aryl substituted by one to five substituents R₁₀, heterocyclyl or heterocyclyl substituted by one to five substituents R₁₀;
each R₁₀ is independently cyano, nitro, amino, hydroxyl, halogen, C₁-C₆ alkyl, C₁-C₆ haloalkyl, C₂-C₆ alkenyl, C₂-C₆ haloalkenyl, C₂-C₆ alkynyl, C₂-C₆ haloalkynyl, C₃-C₆ cycloalkyl, C₃-C₆ halocycloalkyl, C₁-C₆ alkoxy, C₁-C₆ haloalkoxy, C₁-C₆ alkylthio, C₁-C₆ haloalkylthio, C₁-C₆ alkylsulfinyl, C₁-C₆ haloalkylsulfinyl, C₁-C₆ alkylsulfonyl, C₁-C₆ haloalkylsulfonyl, N-C₁-C₆ alkylamino, N,N-di-(C₁-C₆ alkyl)amino, N,N-di-(C₁-C₆ alkyl)aminocarbonyl, N,N-di-(C₁-C₆ alkyl)aminosulfonyl, C₁-C₆ alkylcarbonyl, C₁-C₆ alkylcarbonyloxy, C₁-C₆ alkoxycarbonyl, C₁-C₆ alkylcarbonylamino;
or salts or N-oxides thereof.

2. A compound according to claim 1, wherein
Q is (I');
Both W are O;
R₁ is H, trifluoromethyl, cyano, halogen or methyl;
R₂ is H, trifluoromethyl, cyano, methoxy, halogen or methyl;
X is halogen, C₁-C₆haloalkyl or cyano;
R₃ is H or C₁-C₆alkyl;
R₅, R₆, R₇ and R₈ are independently hydrogen or methyl;
R₉ is hydrogen, C₁-C₆alkyl, C₁-C₆haloalkyl, C₂-C₆ alkenyl, C₂-C₆alkynyl, C₃-C₆cycloalkyl, benzyl, or R₉ is C₁-C₆ alkyl substituted by one or more C₁-C₆alkoxy, C₁-C₆alkylthio.

3. A compound according to claim 2, wherein R₃ is hydrogen.

4. A compound according to any one of claims 2 or 3, wherein R₉ is hydrogen, methyl, ethyl, n-propyl or iso-propyl.

5. A compound according to claim 1, wherein
Q and R₃ form cyclic group (I");
Both W are O;
R₁ is H, trifluoromethyl, cyano, halogen or methyl;
R₂ is H, trifluoromethyl, cyano, methoxy, halogen or methyl;
X is halogen, C₁-C₆haloalkyl or cyano;
R₅, R₆, R₇ and R₈ are independently hydrogen or methyl.

6. A compound according to any one of claims 1 to 5, wherein X is bromine, chlorine, trifluoromethyl or cyano.

7. A compound according to any one of claims 1 to 6, wherein R₁ and R₂ are hydrogen.

8. A compound according to any one of claims 1 to 7, wherein R₅, R₆, R₇ and R₈ are hydrogen.

9. A plant growth regulator or seed germination promoting composition, comprising a compound according to any one of the preceding claims, and an agriculturally acceptable formulation adjuvant.

10. A method for regulating the growth of plants at a locus, wherein the method comprises applying to the locus a plant growth regulating amount of a compound according to any one of claims 1 to 8, or the composition according to claim 9.

11. A method for promoting the germination of seeds comprising applying to the seeds, or a locus containing seeds, a seed germination promoting amount of a compound according to any one of claims 1 to 8, or the composition according to claim 9.

12. A method for controlling weeds comprising applying to a locus containing the seeds a seed germination promoting amount of a compound according to any one of claims 1 to 8, or the composition according to claim 9, allowing the seeds to germinate, and then applying to the locus a post-emergence herbicide.

13. Use of a compound of formula I according to any one of claims 1 to 8 as a plant growth regulator or a seed germination promoter.